Polyomavirus BK nephropathy is an increasingly recognized complication of organ transplantation. It is associated with significant morbidity & 20-50% risk of graft loss. We propose to study how the immune system reacts to BK virus infection. The ultimate long-term goal of our proposal is to generate data, which will help in the development of vaccines & immunotherapy protocols against this disease. The study will have the following specific aims: (1) To determine the influence of donor and host recipient serologic status on the clinical course of BK virus infection after liver and kidney transplantation. (2) To characterize the anti-BKV T-helper (Th) response in BK virus infection in (a) healthy subjects, (b) kidney transplant recipients, and (c) liver transplant recipients (3) To characterize the T-cytotoxic cell response to BK virus in (a) healthy subjects, (b) kidney transplant recipients, and (c) liver transplant recipients. The information generated during the course of this study will permit earlier diagnosis of BK virus infection infection, prior to advanced and potentially irreversible tissue injury. The research proposed will also promote better understanding of the biologic factors that initiate and perpetuate viral nephropathy. This, in turn, will help us to better predict the clinical course of the disease in individual patients, and help devise more effective forms of anti-viral therapy.